PRIMING T-CELL RESPONSES WITH RECOMBINANT MEASLES VACCINE VECTOR IN A HETEROLOGOUS PRIME-BOOST SETTING IN NON-HUMAN PRIMATES

Monday, 8th of September 2014

[source]Vaccine[|source]

In a recombinant measles vaccine (rMV) vector, an antigen from another pathogen is incorporated into the measles genome. During the replication and transcription of rMV in a cell, the transgene is expressed together with viral proteins and presented to the host immune system, inducing a transgene-specific immune response. Thus a multivalent vaccine vector would induce not only strong immunity and protection against measles but also against another pathogen. A number of different transgenes, including genes from human papilloma virus, SARS coronavirus, West Nile virus, and human and simian immunodeficiency viruses (HIV/SIV), have been stably incorporated into the recombinant measles genome, with demonstrated transgene protein expression.

In this report, the authors evaluated whether recombinant measles vector could enhance immune response when combined with a heterologous Ad5-based vaccine vector. The report documents that  rMV efficiently primes CD8⁺ T cells in a heterologous prime-boost regimen with a suboptimal boosting dose of an adenovirus vector has important implications for vaccine design. More details on findings and recommendations are accessible at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3425710/

 

ABSTRACT

Licensed live attenuated virus vaccines capable of expressing transgenes from other pathogens have the potential to reduce the number of childhood immunizations by eliciting robust immunity to multiple pathogens simultaneously. Recombinant attenuated measles virus (rMV) derived from the Edmonston Zagreb vaccine strain was engineered to express simian immunodeficiency virus (SIV) Gag protein for the purpose of evaluating the immunogenicity of rMV as a vaccine vector in rhesus macaques. rMV-Gag immunization alone elicited robust measles-specific humoral and cellular responses, but failed to elicit transgene (Gag)-specific immune responses, following aerosol or intratracheal/intramuscular delivery. However, when administered as a priming vaccine to a heterologous boost with recombinant adenovirus serotype 5 expressing the same transgene, rMV-Gag significantly enhanced Gag-specific T lymphocyte responses following rAd5 immunization. Gag-specific humoral responses were not enhanced, however, which may be due to either the transgene or the vector. Cellular response priming by rMV against the transgene was highly effective even when using a suboptimal dose of rAd5 for the boost. These data demonstrate feasibility of using rMV as a priming component of heterologous prime-boost vaccine regimens for pathogens requiring strong cellular responses.